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Structure paper

TitleStructure of a volume-regulated anion channel of the LRRC8 family.
Journal, issue, pagesNature, Vol. 558, Issue 7709, Page 254-259, Year 2018
Publish dateMay 16, 2018
AuthorsDawid Deneka / Marta Sawicka / Andy K M Lam / Cristina Paulino / Raimund Dutzler /
PubMed AbstractVolume-regulated anion channels are activated in response to hypotonic stress. These channels are composed of closely related paralogues of the leucine-rich repeat-containing protein 8 (LRRC8) family ...Volume-regulated anion channels are activated in response to hypotonic stress. These channels are composed of closely related paralogues of the leucine-rich repeat-containing protein 8 (LRRC8) family that co-assemble to form hexameric complexes. Here, using cryo-electron microscopy and X-ray crystallography, we determine the structure of a homomeric channel of the obligatory subunit LRRC8A. This protein conducts ions and has properties in common with endogenous heteromeric channels. Its modular structure consists of a transmembrane pore domain followed by a cytoplasmic leucine-rich repeat domain. The transmembrane domain, which is structurally related to connexin proteins, is wide towards the cytoplasm but constricted on the outside by a structural unit that acts as a selectivity filter. An excess of basic residues in the filter and throughout the pore attracts anions by electrostatic interaction. Our work reveals the previously unknown architecture of volume-regulated anion channels and their mechanism of selective anion conduction.
External linksNature / PubMed:29769723
MethodsEM (single particle) / X-ray diffraction
Resolution1.8 - 7.94 Å
Structure data

EMDB-4361:
Cryo-EM density of heteromeric mLRRC8A/C volume-regulated anion channel at 7.94 A resolution
Method: EM (single particle) / Resolution: 7.94 Å

4362

6g8z

EMDB-4362: Cryo-EM density of the pore domain of homomeric mLRRC8A volume-regulated anion channel at 3.66 A resolution
PDB-6g8z: Structure of the pore domain of homomeric mLRRC8A volume-regulated anion channel at 3.66 A resolution
Method: EM (single particle) / Resolution: 3.66 Å

4366

6g9l

EMDB-4366: Cryo-EM density of homomeric mLRRC8A volume-regulated anion channel at 5.01 A resolution
PDB-6g9l: Structure of homomeric mLRRC8A volume-regulated anion channel at 5.01 A resolution
Method: EM (single particle) / Resolution: 5.01 Å

4367

6g9o

EMDB-4367: Cryo-EM density of full-length homomeric mLRRC8A volume-regulated anion channel at 4.25 A resolution
PDB-6g9o: Structure of full-length homomeric mLRRC8A volume-regulated anion channel at 4.25 A resolution
Method: EM (single particle) / Resolution: 4.25 Å

PDB-6fnw:
Structure of a volume-regulated anion channel of the LRRC8 family
Method: X-RAY DIFFRACTION / Resolution: 1.8 Å

Chemicals

ChemComp-EDO:
1,2-ETHANEDIOL / Ethylene glycol

ChemComp-HOH:
WATER / Water

Source
  • mus musculus (house mouse)
KeywordsMEMBRANE PROTEIN / ion channel / leucine-rich repeat domain / Chloride channel / Swelling-activated / VSOAC / Leucine-rich repeat

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